Evidence map›Paper›PMID 40585135›Full record

ArticlemedRxiv : the preprint server for health sciences2025

The Aging Epigenome: Integrative Analyses Reveal Functional Overlap with Alzheimer's Disease.

Wei Zhang, David Lukacsovich, Juan I Young, Lissette Gomez, Michael A Schmidt, Brian W Kunkle, Xi Chen, Eden R Martin, Lily Wang

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Wei ZhangDivision of Biostatistics, Department of Public Health Sciences, University of Miami, Miller School of Medicine, Miami, FL 33136, USA.
David LukacsovichDivision of Biostatistics, Department of Public Health Sciences, University of Miami, Miller School of Medicine, Miami, FL 33136, USA.
Juan I YoungDr. John T Macdonald Foundation Department of Human Genetics, University of Miami, Miller School of Medicine, Miami, FL 33136, USA.
Lissette GomezJohn P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Michael A SchmidtDr. John T Macdonald Foundation Department of Human Genetics, University of Miami, Miller School of Medicine, Miami, FL 33136, USA.
Brian W KunkleDr. John T Macdonald Foundation Department of Human Genetics, University of Miami, Miller School of Medicine, Miami, FL 33136, USA.
Xi ChenDivision of Biostatistics, Department of Public Health Sciences, University of Miami, Miller School of Medicine, Miami, FL 33136, USA.
Eden R MartinDr. John T Macdonald Foundation Department of Human Genetics, University of Miami, Miller School of Medicine, Miami, FL 33136, USA.
Lily WangDivision of Biostatistics, Department of Public Health Sciences, University of Miami, Miller School of Medicine, Miami, FL 33136, USA.ORCID 0000-0002-8311-4251

Funding

Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0M
Integrative Genomic Approaches for Understanding Sex Differences in Alzheimer's DiseaseR01AG062634 · NIA · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI KUNKLE, BRIAN WILLIAM, MARTIN, EDEN R. · 2019 to 2023
$3.8M
New computational tools for understanding and predicting AD via age-associated DNA methylation changesRF1NS128145 · NINDS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI WANG, LILY · 2022 to 2022
$2.0M
New DNA methylation biomarkers for predicting AD and cognitive declineR61NS135587 · NINDS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI WANG, LILY · 2024 to 2025
$1.5M
NIA NIH HHS R01 AG062634NIA NIH HHS U01 AG024904NINDS NIH HHS R61 NS135587NINDS NIH HHS RF1 NS128145
6 · The paper itself

Abstract

Aging is the strongest risk factor for Alzheimer's disease (AD), yet the role of age-associated DNA methylation (DNAm) changes in blood and their relevance to AD remains poorly understood. In this study, we performed a meta-analysis of blood DNAm samples from 475 dementia-free subjects aged over 65 years across two independent cohorts, the Framingham Heart Study (FHS) at Exam 9 and the Alzheimer's Disease Neuroimaging Initiative (ADNI). After adjusting for age, sex, and immune cell type proportions, and correcting for batch effects and genomic inflation, we identified 3758 CpGs and 556 differentially methylated regions (DMRs) consistently associated with aging in both cohorts at a 5% false discovery rate. Our pathway enrichment analyses highlighted immune response, metabolic regulation, and synaptic plasticity, all of which are key biological processes implicated in AD. Moreover, our colocalization analysis revealed 32 genomic regions where shared genetic variants influenced both DNAm and dementia risk. Adjusting for age and other covariate variables, we found roughly one-third of aging-associated CpGs are also associated with AD or AD neuropathology in independent studies external to the ADNI and FHS datasets. Finally, we prioritized 9 aging-associated CpGs, located in promoter regions of

Indexed as

agingAlzheimer’s diseaseDNA methylationepigenetics

Identifiers

PMID40585135
PMCPMC12204410

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.